title: Stress-induced epinephrine levels compromise murine dermal fibroblast activity through β-adrenoceptors.
abstract: Stress-induced catecholamine impairs the formation of granulation tissue acting directly in fibroblast activity; however, the mechanism by which high levels of catecholamines alter the granulation tissue formation is still unclear. Thus, the aim of this study was to investigate how high levels of epinephrine compromise the activity of murine dermal fibroblasts. Dermal fibroblasts isolated from the skin of neonatal Swiss mice were preincubated with α- or β-adrenoceptor antagonists. Thereafter, cells were exposed to physiologically elevated levels of epinephrine or epinephrine plus α- or β-adrenoceptor antagonists, and fibroblast activity was evaluated. The blockade of β1- and β2-adrenoceptors reversed the increase in fibroblast proliferation, ERK 1/2 phosphorylation, myofibroblastic differentiation and the reduction of collagen deposition induced by epinephrine. In addition, the blockade of β3-adrenoceptors reversed the increase in fibroblast proliferation and nitric oxide synthesis as well as the reduction of fibroblast migration, AKT phosphorylation and active matrix metalloproteinase-2 expression induced by epinephrine. However, the blockade of α1- and α2-adrenoceptors did not alter the effects of epinephrine on the activity of murine dermal fibroblasts. In conclusion, high levels of epinephrine directly compromise the activity of neonatal mouse skin fibroblasts through the activation of β1-, β2- and β3-adrenoceptors, but not through α1- and α2-adrenoceptors.
authors.affiliation: Department of Histology and Embryology, Rio de Janeiro State University, Rio de Janeiro, Brazil.
authors.forename: Bruna
authors.initials: B
authors.lastname: Romana-Souza
authors.forename: Marcela
authors.initials: M
authors.lastname: Otranto
authors.forename: Taís Fontoura
authors.initials: TF
authors.lastname: Almeida
authors.forename: Luis Cristóvão
authors.initials: LC
authors.lastname: Porto
authors.forename: Andréa
authors.initials: A
authors.lastname: Monte-Alto-Costa
mesh_terms: D000199:Actins / Q000378:metabolism; D058673:Adrenergic beta-3 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D020405:Dermis / Q000166:cytology*; D004837:Epinephrine / Q000378:metabolism / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006909:Hydroxyproline / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009025:Morpholines / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009573:Nitrites / Q000378:metabolism; D010646:Phentolamine / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: C097869:3-(2-ethylphenoxy)-1-(1,2,3,4-tetrahydronaphth-1-ylamino)-2-propanol oxalate; D000199:Actins; D058673:Adrenergic beta-3 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D002867:Chromones; D009025:Morpholines; D009573:Nitrites; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C544013:alpha-smooth muscle actin, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D011433:Propranolol; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2; D006909:Hydroxyproline; D019331:NG-Nitroarginine Methyl Ester; D004837:Epinephrine; D010646:Phentolamine